NCT04807530 · University of California, San Francisco
Medial-prefrontal Enhancement During Schizophrenia Systems Imaging
(MESSI)
What this study is about
This randomly assigned controlled trial in healthy controls (HC) and patients with schizophrenia (SZ) aims to examine 1) the underlying cognitive and neural cause of self-agency deficits in SZ; 2) the responsiveness to a novel navigated repetitive transcranial magnetic stimulation (nrTMS) target in the medial/superior prefrontal cortex (mPFC); and 3) how modulation of mPFC activity impacts the larger self-agency network to mediate changes in self-agency judgments. Our overall hypothesis is that increased mPFC excitability by active high-frequency nrTMS in HC and SZ will induce behavioral improvements in self-agency and neural changes in the larger self-agency network that will generalize to improvements in overall cognition, symptoms and daily functioning, and will likely lead to the development of new effective neuromodulation therapies in patients with schizophrenia.
View original scientific description
This randomized controlled trial in healthy controls (HC) and patients with schizophrenia (SZ) aims to examine 1) the underlying cognitive and neural cause of self-agency deficits in SZ; 2) the responsiveness to a novel navigated repetitive transcranial magnetic stimulation (nrTMS) target in the medial/superior prefrontal cortex (mPFC); and 3) how modulation of mPFC activity impacts the larger self-agency network to mediate changes in self-agency judgments. Our overall hypothesis is that increased mPFC excitability by active high-frequency nrTMS in HC and SZ will induce behavioral improvements in self-agency and neural changes in the larger self-agency network that will generalize to improvements in overall cognition, symptoms and daily functioning, and will likely lead to the development of new effective neuromodulation therapies in patients with schizophrenia.
Interventions
DEVICE
TMS
The investigators will use the NEXSTIM NAVIGATED BRAIN STIMULATION (NBS) SYSTEM to apply 10 Hz nrTMS to healthy controls (HC) and schizophrenia patients (SZ)
Primary outcome measures
Self-Agency Behavioral Change during Reality Monitoring after TMS vs Baseline (metrics of accuracy)
Time frame: From baseline, to immediately after TMS, up to 1 week
Change in retrieval accuracy of self-generated information during reality monitoring task from baseline to post-TMS. No scales used.
Self-Agency Behavioral Change during Speech Monitoring after TMS vs Baseline (metrics of speech perturbation units)
Time frame: From baseline, to immediately after TMS, up to 1 week
Change in speech corrective responses during altered vs. unaltered auditory feedback, measured in units of speech perturbation (cents) from baseline to post-TMS. No scales used.
MEGI Neural Activity Change related to Self-Agency during Reality Monitoring after TMS vs Baseline (metrics of neural beta activation units)
Time frame: From baseline, to immediately after TMS, up to 1 week
Whole-brain neural activity change related to self-agency by contrasting oscillatory activity during encoding and retrieval of self-generated information with encoding and retrieval of externally-derived information (with focus on mPFC and parietal cortices as our region-of-interest (ROI)), measured in beta weights neural signal change from baseline to post-TMS. No scales used.
MEGI Neural Activity Change related to Self-Agency during Speech Monitoring after TMS vs Baseline (metrics of neural beta activation units)
Time frame: From baseline, to immediately after TMS, up to 1 week
Whole-brain neural activity related to self-agency by contrasting oscillatory activity related to speech onset during altered auditory feedback with activity related to speech onset during unaltered auditory feedback (with focus on mPFC and parietal cortices for ROI analyses) measured in beta weights neural signal change from baseline to post-TMS. No scales used.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- All Subjects:
- Good general physical health
- English is first language
- No neurological disorder
- Meets MRI criteria
- No current alcohol or substance use disorder Schizophrenia participants:
- Schizophrenia diagnosis of any illness duration,
- Clinical stability, defined as 12 weeks outpatient status and 4 weeks low to moderate dose of antipsychotic medication (\<1000 mg. chlorpromazine equivalents), plus stable doses of all other psychotropic medications
Exclusion criteria
- All Subjects:
- Implanted metallic parts of implanted electronic devices
- Pregnant or trying to become pregnant
- Any condition that would prevent the subject from giving voluntary informed consent
- Scalp wounds or infections
- Claustrophobia precluding MRI
- Ongoing seizures
- Neurological disorder
Where
- San Francisco, California
Collaborators
National Institute of Mental Health (NIMH)
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Aug 29, 2025 · Source of record for eligibility and locations